Cryptococcus neoformans chitin synthase 3 plays a critical role in dampening host inflammatory responses

Cryptococcus neoformans is the most common disseminated fungal pathogen in AIDS patients, resulting in ∼200,000 deaths each year. There is a pressing need for new treatments for this infection, as current antifungal therapy is hampered by toxicity and/or the inability of the host’s immune system to aid in resolution of the disease. An ideal target for new therapies is the fungal cell wall. The cryptococcal cell wall is different from the cell walls of many other pathogenic fungi in that it contains chitosan. Strains that have decreased chitosan are less pathogenic and strains that are deficient in chitosan are avirulent and can induce protective responses. In this study, we investigated the host responses to a chs3Δ strain, a chitosan-deficient strain, and found that mice inoculated with the chs3Δ strain all died within 36 h and that death was associated with an aberrant hyperinflammatory immune response driven by neutrophils, indicating that chitosan is critical in modulating the immune response to Cryptococcus.Cryptococcus neoformans infections are significant causes of morbidity and mortality among AIDS patients and the third most common invasive fungal infection in organ transplant recipients. One of the main interfaces between the fungus and the host is the fungal cell wall. The cryptococcal cell wall is unusual among human-pathogenic fungi in that the chitin is predominantly deacetylated to chitosan. Chitosan-deficient strains of C. neoformans were found to be avirulent and rapidly cleared from the murine lung. Moreover, infection with a chitosan-deficient C. neoformans strain lacking three chitin deacetylases (cda1Δcda2Δcda3Δ) was found to confer protective immunity to a subsequent challenge with a virulent wild-type counterpart. In addition to the chitin deacetylases, it was previously shown that chitin synthase 3 (Chs3) is also essential for chitin deacetylase-mediated formation of chitosan. Mice inoculated with the chs3Δ strain at a dose previously shown to induce protection with the cda1Δcda2Δcda3Δ strain die within 36 h after installation of the organism. Mortality was not dependent on viable fungi, as mice inoculated with a heat-killed preparation of the chs3Δ strain died at the same rate as mice inoculated with a live chs3Δ strain, suggesting that the rapid onset of death was host mediated, likely caused by an overexuberant immune response. Histology, cytokine profiling, and flow cytometry indicate a massive neutrophil influx in the mice inoculated with the chs3Δ strain. Mice depleted of neutrophils survived chs3Δ inoculation, indicating that death was neutrophil mediated. Altogether, these studies lead us to conclude that Chs3, along with chitosan, plays critical roles in dampening cryptococcus-induced host inflammatory responses

Superimposed Pilots are Superior for Mitigating Pilot Contamination in Massive MIMO

In this paper, superimposed pilots are introduced as an alternative to time-multiplexed pilot and data symbols for mitigating pilot contamination in massive multiple-input multiple-output (MIMO) systems. We propose a non-iterative scheme for uplink channel estimation based on superimposed pilots and derive an expression for the uplink signal-to-interference-plus-noise ratio (SINR) at the output of a matched filter employing this channel estimate. Based on this expression, we observe that power control is essential when superimposed pilots are employed. Moreover, the quality of the channel estimate can be improved by reducing the interference that results from transmitting data alongside the pilots, and an intuitive iterative data-aided scheme that reduces this component of interference is also proposed. Approximate expressions for the uplink SINR are provided for the iterative data-aided method as well. In addition, we show that a hybrid system with users utilizing both time-multiplexed and superimposed pilots is superior to an optimally designed system that employs only time-multiplexed pilots, even when the non-iterative channel estimate is used to build the detector and precoder. We also describe a simple approach to implement this hybrid system by minimizing the overall inter and intra-cell interference. Numerical simulations demonstrating the performance of the proposed channel estimation schemes and the superiority of the hybrid system are also provided

Cryptococcus at work: Gene expression during human infection

Meningitis is a frequent manifestation of infection due to Cryptococcus neoformans and a major cause of increased morbidity in patients with AIDS. Numerous in vitro gene expression and genetic studies of the fungus have predicted a myriad of genes, pathways, and biological processes that may be critical for pathogenesis, and many studies using animal models have supported the role of these processes during infection. However, the relevance of these hypotheses based on in vitro and animal models has often been questioned. A recent study by Chen et al. [Y. Chen, D. L. Toffaletti, J. L. Tenor, A. P. Litvintseva, C. Fang, T. G. Mitchell, T. R. McDonald, K. Nielsen, D. R. Boulware, T. Bicanic, and J. R. Perfect, mBio 5(1):e01087-13, 2014] represents an important step in understanding the cryptococcal response during human infection

A Rare Case of Lung Hypoplasia, Cardiac Anomalies and Ovarian Tumour in a Patient with MRKH Syndrome

Hypoplasia of the lung is an uncommon congenital abnormality of the respiratory system in contrast to Pulmonary agenesis. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is the congenital absence of the upper two-thirds of the vagina and uterus with normal secondary sexual characteristics, ovary, and normal karyotype. Here we describe a case of left lung hypoplasia and congenital cardiac malformations with MRKH syndrome and Leiomyoma of the ovary. A 31-year-old female presented with cough with expectoration, left side chest pain and breathlessness for four years to Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER). She was evaluated for amenorrhea and diagnosed as MRKH syndrome and the patient underwent right side oophorectomy for right ovarian torsion with a tumour. Computed Tomography Pulmonary Angiogram (CTPA) and fiberoptic endoscopy were suggestive of left lung hypoplasia, and the patient was advised symptomatic treatment for lung hypoplasia and planned for vaginoplasty. Keywords: Pulmonary hypoplasia, Infertility, Mullerian aplasia, congenital bronchiectasis, Left-sided superior vena cava, ovarian Leiomyoma

Design Qualification of an External Store for a Fighter Aircraft

Defence Avionics Research Establishment (DARE) has designed and developed an externalstore for fitment on a fighter aircraft. The external store has the poded structure and can be usedfor installation of a variety of payloads up to 250 kg. The mechanical details of the electronicsto be fitted inside the pod can be worked out as per application. The pod has been designedkeeping this in mind and based on the functional, mechanical, structural, and aerodynamicrequirements. The designed and fabricated pod has undergone various qualification tests. Thepaper brings out the details of the pod design, and the various structural and environmentalqualification tests carried out. The pod thus designed and qualified has been validated throughcarriage trials by fitting the pod on the platform intended for it. The pod is likely to be inductedinto the Services shortly